荧光分光光度法检测半乳糖化白蛋白磁性阿霉素纳米粒在大鼠体内分布的研究

目的观察由半乳糖化白蛋白磁性纳米粒运载的阿霉素经舌静脉给药后在大鼠体内的的分布状况.方法全部大鼠随机分为四组,经舌静脉,按分组分别注射相应药物,剂量均为阿霉素2.5 mg/kg体重.取全血、心、肺、肝、脾、肾.全血制成血浆,器官组织制成匀浆,盐酸乙醇法提取阿霉素,用荧光光度计测量.结果静脉注射同等剂量、不同剂型的阿霉素药物后,阿霉素在器官中的蓄积程度从高到低:肝:D靶肝＞D非靶肝、C＞B＞A;心脏、肾、血浆:A＞B＞D、C;脾:B＞A、C、D;肺:B＞A＞C、D.磁性阿霉素白蛋白纳米粒注入体内后,在心、肺、肝、脾、肾中的药物浓度在15～30min达峰值,而半乳糖化后,阿霉素的药物峰值提前到5 min或之前.外加磁场和未加磁场的半乳糖化白蛋白磁性阿霉素纳米粒组的药物靶向指数和药物选择指数是均高于磁性白蛋白纳米粒.结论磁性阿霉素白蛋白纳米粒经半乳糖化后,可显著增强阿霉素对肝脏的靶向性,并显著降低心、肺、脾、肾、血浆肝外器官的组织阿霉素浓度.利用外加磁场,可提高阿霉素在肝脏特定部位蓄积的能力.因此,静脉注射半乳糖化白蛋白磁性阿霉素纳米粒是可行的.     

Pressure distribution and perceived comfort in casual footwear

The aim of this investigation was to establish the relationship between short-term perceived comfort and pressure distribution on the dorsal and plantar surfaces of the foot, while walking in a range of commercially available casual footwear. The study was carried out in the biomechanics laboratory of Manchester Metropolitan University using 15 male subjects without foot pathology. Perceived upper and plantar comfort were measured using a specially designed questionnaire, while dorsal and plantar pressure distributions were measured using a rectangular sensor pad recording at 30 Hz and a Mikro-EMED insole recording at 100 Hz respectively. Analysis of variance tests were used to determine differences in perceived comfort and pressure distribution between three pairs of shoes. The findings of this study suggest that an increase in total plantar force and force-time integral may relate to a decrease in perceived plantar comfort. For the three shoes examined in this study, overall peak plantar pressure, the pressure-time integral, and total plantar area did not appear to be linked to perceived plantar comfort. Findings for the shoe upper indicate that decreased dorsal forces and pressures may be related to decreased upper comfort. These findings suggest that the measurement of pressure distribution at the foot-shoe interface could be a useful tool in identifying the causes of discomfort in footwear.     

~(125)Ⅰ眼镜蛇毒及抗眼镜蛇毒血清在小白鼠体内分布的比较观察

用氯胺-T法125I标记眼镜蛇毒示踪液及抗眼镜蛇毒血清。小白鼠分二组，用125I-眼镜蛇毒、125I-抗眼镜蛇毒血清分别给小白鼠尾静脉注射，于注射后的不同时间测定血、颈部肌肉、肝、肺、肾、心等脏器放射性分布。结果发现：125I-眼镜蛇毒在肌肉及肝、肺等器官中于注射后2小时过高峰，在肾脏中浓度高，在脑未见放射性分布，抗眼镜蛇毒血清与眼镜蛇毒分布相似但在肌肉及肺脏有更高的分布。证明抗眼镜蛇毒血清能跟踪分布眼镜蛇毒。     

Reflection on the geographic distribution of multiple sclerosis in France

The geographic distribution of multiple sclerosis within the 95 Départements and the 21 Régions of France was defined from a 1986 nationwide prevalence series derived from questionnaires. This indicated a significant clustering of high frequency regions in the northeastern part of the country with most significantly low areas in the south and west. Distributions were similar to those for MS death rates by Département and Région for 1968–1977, indicating geographic stability over time; but there was also evidence of diffusion over time. The 1986 prevalence distribution was also compared with all published prevalence rates for communities of France. From all these resources we conclude that all of France falls within the "high frequency zone" for MS, that the nationwide prevalence rate is at least 50 per 100000 population, and that there is evidence of geographic clustering of the disease with temporal spread of the cluster.     

Disposition of 14C-dapoxetine in rats: Complementary experiments with whole-body autoradiographic and tissue dissection techniques

Tissue distribution studies, utilizing whole-body autoradiography and organ dissection techniques, were conducted in male Fischer 344 rats following the oral administration of ¹⁴C-dapoxetine HCl, a potent serotonin reuptake inhibitor. The preliminary study using whole-body autoradiography proved invaluable in locating radioactivity in an organ not usually harvested in a tissue distribution study, namely the preputial gland. Selected organs, based on whole-body autoradiography findings, were dissected from rats and analyzed for radiocarbon content by liquid scintillation counting and for parent drug and N-dealkylated metabolites by extraction and HPLC analysis. Highest concentrations of radiocarbon were observed in the organs of absorption and elimination (ileum, cecum, stomach, duodenum, liver, colon, and kidney) but notable quantities were observed in the lung and preputial and Harderian glands. Most tissues had returned to background radioactive levels 72 h after dosing but persistent concentrations of radiocarbon were present in the preputial gland and liver one week after the single dose of ¹⁴C-dapoxetine. Analysis by HPLC demonstrated the presence of parent drug and N-desmethyl metabolite (nor-dapoxetine) in those organs examined; however, the majority of the radioactivity remained unidentified.     

Na+ currents near and away from endplates on human fast and slow twitch muscle fibers

Fast and slow twitch muscle fibers have distinct contractile properties. Here we determined that membrane excitability also varies with fiber type. Na⁺ currents (I_NA) were studied with the loose-patch voltage clamp technique on 29 histochemically classified human intercostal skeletal muscle fibers at the endplate border and <200 μm from the endplate (extrajunctional). Fast and slow twitch fibers showed slow inactivation of endplate border and extrajunctional I_NA and had increased I_NA at the endplate border compared to extrajunctional membrane. The voltage dependencies of I_NA were similar on the endplate border and extrajunctional membrane, which suggests thatboth regions have physiclogically similar channels. Fast twitch fibers had larger I_NA on the endplate border and extrajunctional membrane and manifest fast and slow inactivation of I_NA at more negative potentials than slow twitch fibers. For normal muscle, the differences between I_NA on fast and slow twitch fibers might: (1) enable fast twitch fibers to operate at high firing frequencies for brief periods; and (2) enable slow twitch fibers to operate at low firing frequencies for prolonged times. Disorders of skeletal membrane excitability, such as the periodic paralyses and myotonias, may impact fast and slow twitch fibers differently due to the distinctive Na⁺ channel properties of each fiber type. © 1993 John Wiley & Sons, Inc.     

125I-RGD-4CY体内生物学分布与药物代谢动力学研究

目的　研究12 5I标记的整合素αVβ3 拮抗多肽 (12 5I RGD 4CY)在小鼠体内的生物学分布及药物代谢动力学。方法　应用Iodogen法行12 5I标记RGD 4CY多肽 ,经小鼠尾静脉注射给药 ,分别在10、30、6 0、12 0和 2 4 0min不同时相点测量血液及各主要组织器官的放射性浓度 ,计算获得其体内生物学分布与药物代谢动力学数据。结果　RGD 4CY能够被12 5I有效标记 ;给药后在血液、肾脏、肝脏有较高的放射性分布 ,小肠、肺脏、肌肉呈低水平放射性分布 ;其分布相半衰期为 9.17min ,消除相半衰期为831min。结论　静脉注射12 5I RGD 4CY后 ,组织本底能够在较短的时间内达到低水平 ,血药浓度一时间曲线符合二房室模型特征 ,在体内的分布与消除为一级线性动力学过程。     

Evaluating risk factors associated with severe hypoglycaemia in epidemiology studies—what method should we use?

AIMS: To determine the most appropriate regression models to use when assessing risk factors for severe hypoglycaemia and to investigate the impact of model misspecification and its clinical implications. METHODS: A total of 1229 children with Type 1 diabetes (mean age 11.7 years sd 4.1), of which 605 (49.2%) were males, were studied. Prospective assessment of severe hypoglycaemia (an event leading to loss of consciousness or seizure) was made over the 9-year period, 1992-2001. Patients were seen every 3 months and episodes of hypoglycaemia along with clinical data were recorded. Over 70% of children never experienced a severe hypoglycaemic event. Data were analysed using the Poisson regression, negative binomial, zero-inflated Poisson (ZIP) and zero-inflated negative binomial (ZINB) models. The over-dispersion and likelihood ratio statistics were calculated and the analytical methods compared. RESULTS: The Poisson regression model did not fit the data well. The negative binomial and the zero inflated Poisson and negative binomial models fitted the data better than Poisson. CONCLUSIONS: The commonly used Poisson regression models to analyse hypoglycaemia epidemiology may lead to biased parameter estimates and incorrect determination of risk factors for hypoglycaemia. We recommend the use of the negative binomial or zero inflated models to examine any risk factors associated with severe hypoglycaemia. Careful consideration must be given to the interpretation of hypoglycaemia surveys and their analysis.     

Conformation of glycyl residues in globular proteins

Glycine is unique among the amino acids in view of its symmetric nature. While the overall distribution of glycyl residues in the (φ, ø) plane is near-symmetric, there can be certain preferences for the individual conformations. An analysis of the observed glycyl conformations in 70 proteins has been carried out to find the influence of residues adjoining the glycyl residues. For this purpose, the (φ, ø) plane has been divided into two regions: (a) the region in which φ is negative and (b) the region in which φ is positive. The analysis is done in terms of the number of conformations occurring in these regions. It has been found that while the overall percentage distribution of glycyl residues between the positive and the negative φ regions is 54:46, the distribution shows asymmetry when the examples are sorted out in terms of X-Gly and Gly-Y doublets. The asymmetry becomes more prominent when the data are sorted out into triplets X-Gly-Y. Using the available information, it has been possible to designate 25 triplets as P-predominant and 19 as N-predominant. An examination of P-predominant triplets for possible occurrence in β-bends having one of the conformations in the positive φ region shows that only 25% are of this nature. Thus, the P-preference of P-predominant triplets is not an outcome of the bend formation alone and must be an inherent property of these triplets.     

基底动脉缝隙连接蛋白的分布

目的：探讨正常脑血管缝隙连接蛋白的分布。方法：采用RT—PCR、免疫组化方法测定多种缝隙连接蛋白在大白兔基底动脉的表达。结果：(1)RT—PCR发现大白兔基底动脉血管组织中至少存在Xx45、Cx43、Cx40和Cx37四种缝隙连接蛋白mRNA表达；(2)免疫组化证实Cx45和Cx43主要分布于血管内皮，平滑肌细胞间末见Cx45和Cx43的染色。结论：大白兔基底动脉血管组织存在丰富的缝隙连接蛋白的表达，与体内其它弹力血管相比，缝隙连接蛋白的分布模式有其特殊性。